The objective of this research is to determine the three-dimensional structure of human erythrocytic purine nucleoside phosphorylase (PNP), an enzyme that contributes to the degradation of various nucleoside analogues of chemotherapeutic potential in transit through the bloodstream to the desired site of action. Large crystals of PNP that are suitable for high resolution analysis have been grown. The low- and high-resolution crystal structures of the enzyme will be determined by multiple-isomorphous- replacement techniques. The structures of purine, nucleoside and analogue complexes of PNP will also be examined. The long-range goal is to understand the mechanisms by which purine derivatives and their analogues interact with this key enzyme, and to provide structural data that may aid in the development of effective inhibitors of PNP.